Current Research and Activities Dr. Don Kyle, Adjunct Professor of - PowerPoint PPT Presentation

Current Research and Activities Dr. Don Kyle, Adjunct Professor of Pharmacology and Physiology, OSU Center for Health Sciences

National Center for Wellness & Recovery MISSION “To inspire hope and to develop innovative, science-driven treatment interventions to improve the lives of those afflicted by pain and substance use disorders” 2

Ending Addiction and Managing Pain Discovery and approval of new, non-addictive, pain medications has been disappointing. • Pain perception is subjective • Placebo effects are common • Translation from animal models to human has been poor • Addiction mechanisms are not well understood. • Genetic pre-disposition • Childhood trauma • Environmental factors • To end the opioid crisis, scientific research aimed at discovering alternatives to opioids • and elucidating the mechanisms of addiction is required. Pain and addiction biomarkers are urgently needed • New molecular approaches for treating pain are of premiere importance • More options for MAT and reversal of overdose are crucial • 3

Biomarker Research NCWR has unique access to nearly 50,000 bio-samples from consenting patients. • Samples obtained from ~2003-2015 in over 30 clinical protocols • Tested drugs include opioids and non-opioids (time-course) • Blood, DNA, and RNA are cross-referenced to non-confidential patient records • Planning is underway to extend this research asset by collecting additional bio-samples during MAT in the future • Research strategies and identification of collaborators and scientific advisors in progress. • Internal assessments of existing and future NCWR core competencies • Data mining and visualization tools are under consideration • Complementary industrial and academic partners enhance and accelerate NCWR’s mission • Successful research will have broad and significant medical impact. • Translational bio-markers will stimulate new research for opioid alternatives • Pain bio-marker would supplement self-report measures in clinical trials, improving trial outcomes • Predictive bio-markers for risk and/or onset of addiction would benefit patients and physicians • 4

Pain Research 1970-2020 1800-1965 PIONEERING OPIOID BIOLOGY PIONEERING OPIOID CHEMISTRY Morphine, oxycodone, fentanyl, buprenorphine Mu receptor, enkephalin, cell signaling, biotech Opioid Pharmacology New Opioid Pharmacology The discovery of opioid drug molecules does not overlap in • time with the discoveries about their mechanism. BIASED It has always been presumed that opioid analgesia and unwanted Opioid Opioid • OPIOID effects are inseparable. Mu Receptor Mu Receptor Unpublished, “biased opioid” research molecules at NCWR show • analgesic efficacy with reductions in unwanted effects in animal X models. CELLULAR Molecules in this collection may also lead to new MAT treatment • β -Arrestin G Protein SIGNALING options Gastrointestinal Analgesia Unwanted NCWR is well positioned to advance the science in this area and • + Respiratory Analgesia Effects Euphoria make new discoveries that will benefit patients. 5

NCWR-1: A Novel Pre-Clinical Research Molecule with Biased Mu Receptor Signaling NCWR-1 MORPHINE Constipation 1hr time point, s.c. dosing 3hr time point, p.o. dosing % Maximum Possible Effect % Maximum Possible Effect 100 100 Respiratory 75 75 Depression Respiratory Minimally Depression (Hot Plate) (Hot Plate) 50 50 Effective Constipation Analgesic 25 25 Minimally Dose 0 0 Effective Analgesic -25 -25 Dose -50 -50 Vehicle 1 3 10 30 100 Vehicle 1 3 5 10 Dose (mg/kg) Dose (mg/kg) The onset of important opioid side-effects differ significantly between morphine • and NCWR-1 in animal models, despite both being mu receptor agonists. 6

Fighting the Emerging Fentanyl Crisis The 3 rd wave of the opioid crisis is fueled by fentanyl • Fentanyl is particularly dangerous • Mu receptor affinity and duration of action exceed naloxone • ”Designer” analogs of fentanyl are evasive to law enforcement • Inexpensive to prepare without need of opium poppies • Blended into other drugs of abuse without knowledge of the end-user. • Research molecules at the NCWR have profiles that may lead to • Molecule Mu Opioid Receptor Lipophilicity Half-Life K i (nM) GTP γ S GTP γ S AlogP Hours effective alternative treatments for fentanyl overdose EC 50 (nM) E MAX (%) Fentanyl 2.7 133 88 4.05 4-8 Higher affinity to mu opioid receptor 0.5 – 1.5 Naloxone 8.8 >20000 0 2.1 • NCWR-2 0.3 >20000 0 2.7 10 - 12 High CNS penetration • NCWR-3 0.9 >20000 0 3.49 TBD NCWR-4 0.07 >20000 0 3.88 TBD Long duration of action • NCWR-5 0.07 >20000 0 6.07 TBD NCWR-6 0.4 >20000 0 5.13 TBD 7

“Fighting Fire - With Fire”: Research Agreements in Progress with Industry High-sensitivity fentanyl bio-sensor Oral thin film formulation 8

National Center for Wellness & Recovery MISSION “To inspire hope and to develop innovative, science-driven treatment interventions to improve the lives of those afflicted by pain and substance use disorders” Presentation Summary Biomarker research for pain and addiction • Novel mechanisms for pain and MAT treatment • New molecules, delivery systems, and analytical • tools to combat the emerging fentanyl crisis 9

Oklahoma Bureau of Narcotics SEPTEMBER 10, 2020

Integration and E-prescribing • STATUS OF INTEGRATION • 139 ENTITIES IN THE PROCESS OF INTEGRATING • OVER 5,300 PRESCRIBERS BEING INTEGRATED • STATUS OF ELECTRONIC PRESCRIBING • 88% OF PRESCRIPTIONS ARE SUBMITTED ELECTRONICALLY • 5.19% OF PRESCRIPTIONS ARE WRITTEN

100.00% 10.00% 20.00% 30.00% 40.00% 50.00% 60.00% 70.00% 80.00% 90.00% 0.00% Jan-17 Feb-17 Mar-17 Apr-17 May-17 Jun-17 Jul-17 Aug-17 Sep-17 Oct-17 Nov-17 Dec-17 Written Jan-18 Feb-18 Prescription Submission Type Mar-18 Apr-18 Electronic May-18 Jun-18 Jul-18 Aug-18 Sep-18 Fax Oct-18 Nov-18 Dec-18 Telephone Jan-19 Feb-19 Mar-19 Apr-19 May-19 Unspecified Jun-19 Jul-19 Aug-19 Sep-19 Oct-19 Nov-19 Dec-19 Jan-20 Feb-20 Mar-20 Apr-20 May-20 Electronic, 88.39% Written, 5.19% Jun-20 Jul-20 Aug-20 Sep-20

PMP Statistics 2020 year to date DISPENSATION BY DRUG SCHEDULES Opioids 2,416,694 45.3% Schedule 2 Schedule 3 Schedule 4 Schedule 5 Non-Opioid 2,917,528 54.7% Schedule 5 5% Total 5,334,222 100% 2020 year to date Schedule 2 43% HYDROCODONE 977,142 18.3% Schedule 4 40% OXYCODONE 485,807 9.1% TRAMADOL 391,994 7.3% ALPRAZOLAM 384,804 7.2% 5.9% ZOLPIDEM 312,827 Schedule 3 12% 47.8% Total 2,552,574

PMP Statistics Total Rx per Year 10000000 9000000 9145506 8959043 8000000 8388189 8163327 7597205 7000000 7338985 6000000 5000000 5334222 5136904 4000000 3000000 2000000 1000000 0 2017 2018 2019 2020 W/ Buprenorphine W/out Buprenorphine

Opioid Statistics Total Opioid Rx per Year 5000000 4500000 4627292 4440829 4000000 4132423 3907561 3500000 3573979 3315759 3000000 2500000 2416694 2219376 2000000 1500000 1000000 500000 0 2017 2018 2019 2020 W/ Buprenorphine W/out Buprenorphine

Disclaimer • All data was pulled September 9, 2020. • Data is labeled by whether it includes Buprenorphine. • Data is entered by the pharmacy and errors could occur.

LEGISLATIVE UPDATE 9/10/20 Deputy Attorney General Lori Carter

HOUSE BILLS • HB4138 by Representative Kevin Wallace and Senator Roger Thompson • Creates the Opioid Abatement Revolving Fund and the Opioid Abatement Board to disperse opioid grant awards to political subdivisions for the purpose of abating the opioid crisis in Oklahoma • Signed by the Governor on May 21, 2020/effective date August 28, 2020 • HB4140 by Representative Kevin Wallace and Senator Roger Thompson • Appropriates $10.22 million from the Opioid Lawsuit Settlement Fund to the Oklahoma Opioid Abatement Revolving Fund, as created by HB4138 • Signed by the Governor on May 21, 2020/effective date August 28, 2020

SENATE BILLS • SB1718 by Senator John M. Montgomery and Representative Jon Echols Parity legislation - It requires benefits for mental health conditions and substance use • disorders be equal to benefits for treatment of all other conditions and shall be subject to the same preauthorization and utilization review mechanisms and other terms and conditions as all other physical diseases and disorders. • Requires health insurers to meet federal parity guidelines Requires insurers to file an annual report with the Insurance Commissioner to demonstrate • compliance with state and federal parity laws Requires Insurance Commissioner to enforce the parity laws and shall post online redacted • reports submitted and identify noncompliant insurers • Status: Signed by the Governor May 19, 2020/effective Nov. 1, 2020 • SB1915 by Senator Kim David and Representative John Pfeiffer Amends the Physician Assistant Act to provide for physician “delegation” instead of • “supervision” and authorizes physician assistants to provide health care services, provided a practice agreement with an allopathic or osteopathic physician or physicians is in place P .A. is to be considered the primary care provider and services must be reimbursed the • same as if a physician had ordered or provided them Status: Signed by the Governor May 21, 2020/effective Aug. 28, 2020 •